Randomized phase 2 trial of erdafitinib with or without cetrelimab for cisplatin-ineligible metastatic urothelial carcinoma with FGFR alterations

First-line treatment options for cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC) are limited. The multinational noncomparative phase 2 NORSE study evaluated first-line erdafitinib with or without cetrelimab for FGFR-altered mUC in cisplatin-ineligible patients. Primary endpoints were investigator-assessed confirmed overall response rate (ORR) and safety. Eighty-seven patients were randomized and treated (43 erdafitinib; 44 erdafitinib plus cetrelimab). Of 64 patients with PD-L1 expression data, 56 (87.5%) had low levels of PD-L1 expression (combined positive score ≤ 10). Median follow-up was 14.2 months. ORR was 44.2% (95% CI 29.1-60.1) with erdafitinib and 54.5% (38.8-69.6) with erdafitinib plus cetrelimab; grade ≥ 3 treatment-related adverse events occurred in 46.5% and 45.5% of patients in the two groups, respectively. Median duration of response was 9.7 months with erdafitinib and 11.1 months with erdafitinib plus cetrelimab. Median progression-free survival and overall survival were 5.6 months and 16.2 months, respectively, with erdafitinib, and 11.0 months and 20.8 months, respectively, with erdafitinib plus cetrelimab. The authors conclude that first-line erdfitinib monotherapy and erdafitinib plus cetrelimab demonstrated antitumor activity and a manageable safety profile in cisplatin-ineligible patients with FGFR-altered mUC.